Efficient activation of nucleoside phosphoramidites with 4,5-dicyanoimidazole during oligonucleotide synthesis.
A new activator for the coupling of phosphoramidites to the 5'-hydroxyl group during oligonucleotide synthesis is introduced. The observed time to complete coupling is twice as fast with 4, 5-dicyanoimidazole (DCI) as the activator, compared with 1 H -tetrazole. The effectiveness of DCI is thought to be based on its nucleophilicity. DCI is soluble in acetonitrile up to 1.1 M at room temperature and can be used as the sole coupling activator during routine automated solid phase synthesis of oligonucleotides. The addition of 0.1 M N -methylimidazole to 0.45 M 1 H -tetrazole also results in higher product yields during oligonucleotide synthesis than observed with 1 H -tetrazole alone.
Vargeese
C
C
NeXstar Technology Products, 2860 Wilderness Place, Boulder, CO 80301, USA.
Carter
J
J
Yegge
J
J
Krivjansky
S
S
Settle
A
A
Kropp
E
E
Peterson
K
K
Pieken
W
W
D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D005069:Evaluation Studies as Topic; D007093:Imidazoles; D007202:Indicators and Reagents; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D012995:Solubility; D013777:Tetrazoles
C110830:4,5-dicyanoimidazole; D007093:Imidazoles; D007202:Indicators and Reagents; D009705:Nucleosides; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D013777:Tetrazoles; C045574:1H-tetrazole